Prenatal exposure to drinking-water chlorination by-products, cytochrome P450 gene polymorphisms and small-for-gestational-age neonates

Abstract

Genetic susceptibility may modulate chlorination by-products (CBPs) effects on fetal growth, especially genes coding for the cytochrome P450 involved in the metabolism of CBPs and steroidogenesis. In a case-control study of 1432 mother-child pairs, we assessed the association between maternal and child single nucleotide polymorphisms (SNPs) within CYP1A2, CYP2A6, CYP2D6 and CYP17A1 genes and small-for-gestational-age neonates (SGA<10th percentile) as well as interaction between these SNPs and maternal exposure to trihalomethanes or haloacetic acids (HAAs) during the third trimester of pregnancy. Interactions were found between mother and neonate carrying CYP17A1 rs4919687A and rs743572G alleles and maternal exposure to total trihalomethanes or five regulated HAAs species. However, these interactions became non statistically significant after correction for multiple testing. There is some evidence, albeit weak, of a potential effect modification of the association between CBPs and SGA by SNPs in CYP17A1 gene. Further studies are needed to validate these observations.

Keywords: CYP17A1; CYP1A2; CYP2A6; CYP2D6; Chlorination by-products; Gene-environment interaction; Intra-uterine growth restriction; Single nucleotide polymorphism; Small-for-gestational-age.

Fig. 1

Flow Chart starting from the participants to the previous gene-environment study (Levallois et al., 2016) with sample available for DNA extraction to participants to this study (1432 mother-child pairs).